Cytokines are a broad and loose category of small proteins (˜5-20 kDa) that are important in cell signaling. Their release has an effect on the behavior of cells around them. Cytokines are involved in autocrine signaling, paracrine signaling and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors (TNF). Cytokines play an important role in cellular communication. They regulate immunity, inflammation, cell activation, cell migration, cell proliferation, apoptosis, and hematopoiesis. Cytokine inhibitions are also used in treatment of various diseases such as autoimmune diseases (multiple sclerosis and vasculitis), tumor immunotherapy, skin related diseases and rheumatoid arthritis. But cytokine treatment has their fair share of side effects, when released persistently they can result in chronic disease. During the studies of the inflammatory diseases it is found that the certain inflammatory skin diseases have been associated with overproduction of cytokines, alteration in cytokine receptors, or dysregulation of cytokines. The study on the cytokines treatments has proven that the sometimes the cytokines treatment results in deleterious consequences such as flu-like reactions, vascular leak syndrome, fatigue, diarrhea, skin related diseases, thrombocytopenia, shock, respiratory distress, coma, and fatal hypotension.
In order to treat the cytokines related diseases, anti-cytokine therapy is used. The anti-cytokine therapy specifically targets cytokines e.g. TNF and Interleukins (because they are specifically responsible for the inflammation). It is shown in the studies that the inhibition of one cytokine can stop the process of immune system self-activation. The anti-cytokine therapy is used in treatment of skin related diseases such as Psoriasis Eczema, acne lichen planus, atopic dermatitis, and phemphigus. The anti-cytokine therapy has brought a big change in the field of the medicine. But anti cytokine treatment also effects the fundamental protective functions of the body. The anti-cytokine therapy may result in latent microbial infection, demyelinating, secondary autoimmune manifestation, symptoms of lupus erythematosus and inhibition of the cytokine also results in an abundant secretion of interferon α which can lead to thromboembolism. Also, the anti-cytokine therapy is expensive and not every patient can afford this treatment. Another disadvantage with the anti-cytokine therapy is that the it uses oral route for drug administration which is unsuitable for patients which are uncooperative or cannot use their mouth. The drugs administered through oral routes absorbs very slowly in-patient body.
So, there is a need of such novel topical composition which can modulate the cytokines without causing any harm. Alstonine is an alkaloid found in Vinca minor and Aspidosperma which have significance in treating skin related disorder. In the existing arts, alstonine is not defined properly for treatment of skin related problems and modulating the activity of interleukins (IL 17 and IL 12/23).
U.S. Pat. No. 5,290,553A discloses the extraction of alkaloids and their use in treating protozoan induced diseases especially for the treatment of malaria. According to the said disclosure wherein the plant Picralima nitida contains several indole and dihydroindole alkaloids, of which the major ones include akuammiline, akuammidine, akuammine, akuammigine, akuammicine, picraline and picraphylline. The principal alkaloid found in the plant, akuammine, has been shown to be inactive against avian malaria and in clinical trials. This citation does not refer to akuammicine-N-Oxide composition for the treatment of skin related disorders or diseases. Further this citation does not through light on any composition to treat skin relate disorders or diseases. Further this citation does not refer any such composition useful to prepare topical cream to treat skin related disorders or diseases.
WO2007066928A1 discloses an extract of Caesalpinia sappan L. having an angiogenesis inhibition activity and a use of the compound isolated therefrom, more precisely an extract of Caesalpinia sappan L. extracted by using water, alcohol or a mixture thereof, and a use of brazilin, sappanchalcone and brazilein isolated from the extract as an angiogenesis inhibitor. The extract of Caesalpinia sappan L. of the invention and a compound isolated therefrom have angiogenesis inhibition activity, so that they can be effectively used for the prevention and treatment of angiogenesis associated diseases such as vascular diseases, cardiovascular diseases, ophthalmic diseases, chronic inflammatory diseases, dermatological diseases, Alzheimer's disease, obesity and cancer.
US20070048396A1 discloses anti-inflammatory compositions comprising (a) an anti-inflammatory agent selected from the group consisting of olive leaf extract, holly herb, sappan wood, feverfew, and combinations of two or more thereof, and (b) an anti-inflammatory agent comprising at least one lipophilic aminoacid and at least one metal salt. Also provided are personal care products comprising such compositions, and methods of use thereof.
There is no indication from the existing art that alstonine compositions are useful in the treatment of skin related disorders or diseases. Therefore, the present invention discloses novel compositions useful in treating the skin related disorders or diseases.